The New England Journal of Medicine 2010; 363(14):1303-12This is the first phase 2 study to be published for spleen tyrosine kinase (Syk) inhibitor R788 (fostamatinib). This phase 2 study ingestigated the efficacy and safety of fostamatinib in patients with active RA despite long-term treatment with methotrexate. In this 6-month, double-blind, placebo-controlled trial, patients were randomised to receive two doses of R788 (100 mg twice daily or 150 mg once daily) or placebo once or twice daily. Significantly more patients on R788 achieved ACR 20 response at week 1 (placebo 35% vs R788 100 mg twice daily 36%; 150 mg once daily 23%) and month 6 (14%, 67%, 57%). By month 1, R788 had significantly improved DAS28 and this improvement was maintained throughout the study with more patients on R788 achieving DAS28<2.6 at month 6 (7%, 21%, 31%). At month 6, patients on R788 100 mg twice daily had significant improvements in functional assessment of chronic illness (FACIT) fatigue scores and SF-36 physical component summary (PCS) scores. No significant improvement was seen in SF-36 mental health component summary (MCS) scores with R788 or placebo. Adverse events, particularly nausea and diarrhoea, led six patients on placebo and 15 patients on R788 to withdraw from the study. These data showed that Syk inhibition with therapies such as R788 have to potential to offer a new treatment option for RA, with more research necessary.